Mechanistic Insights into the c-MYC G-Quadruplex and Berberine Binding inside an Aqueous Two-Phase System Mimicking Biomolecular Condensates DOI
Susmita Pradhan,

Marco Campanile,

Shubhangi Sharma

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(34), P. 8706 - 8714

Published: Aug. 19, 2024

We investigated the binding between c-MYC G-quadruplex (GQ) and berberine chloride (BCl) in an aqueous two-phase system (ATPS) with 12.3 wt % polyethylene glycol 5.6 dextran, mimicking highly crowded intracellular biomolecular condensates formed via liquid–liquid phase separation. found that ATPS, complex formation is significantly altered, leading to increase affinity a change stoichiometry of respect neat buffer conditions. Thermodynamic studies reveal becomes more thermodynamically favorable ATPS due entropic effects, as strong excluded volume effect inside droplets reduces penalty associated binding. Finally, BCl for GQ higher than those other DNA structures, indicating potential specific interactions. Overall, these findings will be helpful design drugs targeting structures cancer-related biocondensates.

Language: Английский

Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates DOI

Guangle Li,

Chengqian Yuan, Xuehai Yan

et al.

Soft Matter, Journal Year: 2025, Volume and Issue: 21(10), P. 1781 - 1812

Published: Jan. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Language: Английский

Citations

4
Charge Arrangement Determines the Sensitivity of Aggregation Patterns between Peptide-Chains to the Surrounding Ionic Environment DOI
Lei Bao,

Wen-Bin Kang,

Ben‐Chao Zhu

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

The molecular basis for the liquid-liquid phase separation (LLPS) behavior of various biomolecular components in cell is formation multivalent and low-affinity interactions. When content these exceeds a certain critical concentration, molecules will spontaneously coalesce to form new liquid phase; i.e., LLPS occurs. Intrinsically disordered proteins (IDPs) are usually rich amino acids with charged side-chains, thus, LLPS-involving interactions between their side-chains great interest. However, details coalescence such IDPs salt solution still lacking. Here, we focus on two types peptide-chains oppositely extreme arrangements investigate aggregation patterns ionic environments. results show that interaction nonuniform charge arrangement sequences more sensitive surrounding cationic environment, Na+ ions likely cause ASP residues compared Mg2+ ions. As concentration increases, electrostatic gradually converted into negative-negative acid network bridged by ions, while positive charge-rich regions strongly inclined be exposed solvent environment gain greater freedom movement. Simultaneously, this effect reach saturation further increase concentration. present study enriches insights dominant factors phenomena at atomic level, which hopefully inspire design application targeted future.

Language: Английский

Citations

0
Accelerated amyloid fibril formation at the interface of liquid–liquid phase‐separated droplets by depletion interactions DOI Creative Commons
K. Yamaguchi, Joji Mima, Kichitaro Nakajima

et al.

Protein Science, Journal Year: 2025, Volume and Issue: 34(2)

Published: Jan. 28, 2025

Abstract Amyloid fibril formation of α‐synuclein (αSN) is a hallmark synucleinopathies. Although the previous studies have provided numerous insights into molecular basis αSN amyloid formation, it remains unclear how self‐assembles fibrils in vivo. Here, we show that accelerated presence two macromolecular crowders, polyethylene glycol (PEG) (MW: ~10,000) and dextran (DEX) ~500,000), with maximum at approximately 7% (w/v) PEG DEX. Under these conditions, crowders induce two‐phase separation upper lower DEX phases small number liquid droplets phases, respectively. Fluorescence microscope images revealed interfaces phase are major sites formation. We consider depletion interactions working micro phase‐segregated state systems causes condensation interface between solute droplets, resulting Ultrasonication further both confirming droplet‐dependent Similar PEG/DEX‐dependent was observed for β peptide. In contrast, 2 ‐microglobulin or hen egg white lysozyme native fold suppressed PEG/DEX mixtures, suggesting work adversely depending on whether protein unfolded folded.

Language: Английский

Citations

0
Mechanism of amyloid fibril formation triggered by breakdown of supersaturation DOI Creative Commons

Keiichi Yamaguchi,

Kichitaro Nakajima, Hirotsugu Ogi

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1)

Published: Feb. 3, 2025

Language: Английский

Citations

0
ATP‐Regulated Formation of Transient Peptide Amphiphiles Superstructures DOI Creative Commons
David Cappelletti, Federico Lancia, Andrea Basagni

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Self‐assembly of biotic systems serves as inspiration for the preparation synthetic supramolecular assemblies to mimic structural, temporal, and functional aspects living systems. Despite peptide amphiphiles (PAs) being widely studied in context biomimetic bioactive nanomaterials, very little is currently known about reversible spatiotemporal control their hierarchical self‐assemblies. Here, it shown that PA‐based nanofibers can transiently form superstructures, through binding with oppositely charged adenosine triphosphate (ATP), leading charge screening stabilization bundled nanofibers. Enzymatic hydrolysis ATP monophosphate phosphates causes disassembly superstructures recovery individual The lifetime be controlled by adjusting concentration either or enzyme. role formation PA has on chemical reactivity catalysis also evaluated. It observed superstructuration responsible downregulation activity, which then recovered gradual bundles. These results demonstrate potential self‐assembly modulate nanostructures.

Language: Английский

Citations

0
Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain DOI Creative Commons
Wojciech Puławski, Robert Dec, Wojciech Dzwolak

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(4), P. 2025 - 2033

Published: March 25, 2024

Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone vivo at insulin injection sites. We have recently shown that dominant forces driving self-assembly fibrils are likely to arise from intermolecular interactions involving N-terminal segment A-chain (ACC1–13). Here, we study how proline substitutions within pilot GIVEQ sequence this fragment affect its propensity aggregate both neutral acidic environments. In reasonable agreement with silico prediction based on Cordax algorithm, positions 3, 4, 5 turn out be very effective preventing according thioflavin T-fluorescence-based kinetic assay, infrared spectroscopy, atomic force microscopy (AFM). Since valine glutamate side chains strongly involved receptor, focused possible implications Q → P substitution for insulin's stability receptor. To end, comparative molecular dynamics (MD) simulations Q5P mutant wild-type were carried free receptor-bound (site 1) monomers. The results point mild destabilization vis à monomer, well partial preservation key contacts complex between discuss these findings context design aggregation-resistant analogues retaining hormonal activity.

Language: Английский

Citations

2
Unraveling the Hydration Dynamics of the ACC1-13K24-ATP System: From Liquid-to-Droplet to-Amyloid Fibril DOI Creative Commons
Sampad Bag, Robert Dec, Simone Pezzotti

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(22), P. 3863 - 3870

Published: Sept. 11, 2024

Language: Английский

Citations

2
Understanding and fine tuning the propensity of ATP-driven liquid–liquid phase separation with oligolysine DOI
Qiang Zhu, Yongxian Wu, Ray Luo

et al.

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: 26(14), P. 10568 - 10578

Published: Jan. 1, 2024

Liquid–liquid phase separation (LLPS) plays a pivotal role in the organization and functionality of living cells.

Language: Английский

Citations

1
Mechanistic Insights into the c-MYC G-Quadruplex and Berberine Binding inside an Aqueous Two-Phase System Mimicking Biomolecular Condensates DOI
Susmita Pradhan,

Marco Campanile,

Shubhangi Sharma

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(34), P. 8706 - 8714

Published: Aug. 19, 2024

We investigated the binding between c-MYC G-quadruplex (GQ) and berberine chloride (BCl) in an aqueous two-phase system (ATPS) with 12.3 wt % polyethylene glycol 5.6 dextran, mimicking highly crowded intracellular biomolecular condensates formed via liquid–liquid phase separation. found that ATPS, complex formation is significantly altered, leading to increase affinity a change stoichiometry of respect neat buffer conditions. Thermodynamic studies reveal becomes more thermodynamically favorable ATPS due entropic effects, as strong excluded volume effect inside droplets reduces penalty associated binding. Finally, BCl for GQ higher than those other DNA structures, indicating potential specific interactions. Overall, these findings will be helpful design drugs targeting structures cancer-related biocondensates.

Language: Английский

Citations

0